IRIBARREN PABLO
Congresos y reuniones científicas
Título:
Study of autophagy response in neoplastic CLL cells
Autor/es:
ARROYO, DS; RODRIGUEZ, CM; BUSSI, C; PERALTA RAMOS, JM; IRIBARREN, P
Lugar:
Mar del Plata
Reunión:
Congreso; LXIV reunion anual. Sociedad Argentina de Inmunologia (SAI) SAIC; 2016
Institución organizadora:
SAI -SAIC
Resumen:
Chronic Lymphocytic Leukemia (CLL) is a disease characterized
by the clonal proliferation and accumulation of mature, typically
CD5-positive B-cells within the blood, bone marrow, lymph
nodes, and spleen. Leukemic transformation is initiated by alterations
that impair apoptosis of clonal B-cells. The pathway engaged
in programmed cell death involves several Bcl-2 family proteins.
Alternatively, Bcl-2?family proteins have antiautophagic function.
In this regard, the autophagy response has dual phenotype in
cancer depending of the type of tumor cells. This mechanism can
be used for prolonging survival, or for cell death, as well. However,
little is known the role of this degradative process in CLL-B cells.
In previously studies, we observed that Rapamycin (mTOR inhibi -
tor) modulates B cell death induced by Fludarabin. We therefore,
performed an analysis of LC3B expression to evaluate autophagy
induction, in peripheral blood mononuclear cells (PBMC) isolated
from CLL-patients. We stimulated PBMC with Rapamycin and
observed an increased expression of LC3B II, which correlated
with the level of cell death in a co-culture with Rapamycin and
Fludarabin. Moreover, when we used another mTOR inhibitor
(PP242) to stimulate PBMC, we observed higher levels of LC3B
II compared to Rapamycin. These preliminary experiments are
being assayed in others CLL patient samples and also we plan to
evaluate cell death using PP242 plus Fludarabin. These preliminary results may provide important clues to define new strategies
for leukemia therapy
by the clonal proliferation and accumulation of mature, typically
CD5-positive B-cells within the blood, bone marrow, lymph
nodes, and spleen. Leukemic transformation is initiated by alterations
that impair apoptosis of clonal B-cells. The pathway engaged
in programmed cell death involves several Bcl-2 family proteins.
Alternatively, Bcl-2?family proteins have antiautophagic function.
In this regard, the autophagy response has dual phenotype in
cancer depending of the type of tumor cells. This mechanism can
be used for prolonging survival, or for cell death, as well. However,
little is known the role of this degradative process in CLL-B cells.
In previously studies, we observed that Rapamycin (mTOR inhibi -
tor) modulates B cell death induced by Fludarabin. We therefore,
performed an analysis of LC3B expression to evaluate autophagy
induction, in peripheral blood mononuclear cells (PBMC) isolated
from CLL-patients. We stimulated PBMC with Rapamycin and
observed an increased expression of LC3B II, which correlated
with the level of cell death in a co-culture with Rapamycin and
Fludarabin. Moreover, when we used another mTOR inhibitor
(PP242) to stimulate PBMC, we observed higher levels of LC3B
II compared to Rapamycin. These preliminary experiments are
being assayed in others CLL patient samples and also we plan to
evaluate cell death using PP242 plus Fludarabin. These preliminary results may provide important clues to define new strategies
for leukemia therapy
